C-reactive protein enhances activation of coagulation system and inflammatory response through dissociating into monomeric form in antineutrophil cytoplasmic antibody-associated vasculitis.
C-reactive protein enhances activation of coagulation system and inflammatory response through dissociating into monomeric form in antineutrophil cytoplasmic antibody-associated vasculitis.
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C反应蛋白在抗中性粒细胞胞浆抗体相关性血管炎中通过解离成单体形式增强凝血系统的激活和炎症反应
DOI：
10.1186/s12865-015-0077-0
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发表时间：
2015-03-03
期刊：
影响因子：
3
通讯作者：
Wang BL
中科院分区：
文献类型：
--
作者：
Xu PC;Lin S;Yang XW;Gu DM;Yan TK;Wei L;Wang BL
背景C反应蛋白（CRP）通过从五聚体CRP（pCRP）解离为修饰或单体CRP（mCRP）而发挥促血栓形成作用。然而，尽管已确定抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）患者静脉血栓栓塞（VTE）的高患病率，但尚不清楚高水平的循环pCRP是否可能导致AAV的这种高凝状态。ANCA可诱导中性粒细胞胞外陷阱（NETs）的产生。本研究探讨了NETs依赖的pCRP生成mCRP的过程，以及mCRP对AAV激活凝血系统和炎症反应的影响。ANCA诱导的网状中性粒细胞与含mCRP（60 μg/mL）的富血小板血浆（PRP）静态孵育后，表达CD 62 p的血小板比例显著增加，而与含pCRP（60 μg/mL）的PRP静态孵育后，未观察到血小板CD 62 p表达的增加。在流动条件下，灌注固定化ANCA诱导的网状中性粒细胞与pCRP含有PRP引起血小板活化和mCRP沉积。新产生的mCRP诱导ANCA诱导的网状中性粒细胞上的血小板活化，增强D-二聚体的形成，并增强高迁移率族蛋白1的分泌由platelet.ConclusionsUnder流动条件下，ANCA诱导的网状中性粒细胞可以激活血小板，然后促进活化的血小板上的mCRP的形成。然后，新产生的mCRP可以进一步增强血小板活化、血栓形成过程和炎症反应。因此，高水平的循环pCRP不仅是判断疾病活动性的敏感指标，而且参与了AAV的病理生理过程。
BackgroundC-reactive protein (CRP) exerts prothrombotic effects through dissociating from pentameric CRP (pCRP) into modified or monomeric CRP (mCRP). However, although the high prevalence of venous thromboembolism (VTE) in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been identified, it remains unclear whether the high levels of circulating pCRP potentially contribute to this hypercoagulable state in AAV. ANCA can induce the generation of neutrophil extracellular traps (NETs). In this study, the NETs-dependent generation of mCRP from pCRP and the influences of mCRP on the activation of coagulation system and inflammatory response in AAV were investigated.ResultsNETs were induced after TNF-α primed neutrophils were incubated with ANCA-containing IgG. After ANCA-induced netting neutrophils were incubated statically with platelet-rich plasma (PRP) containing mCRP (60 μg/mL), the proportion of platelets expressing CD62p increased significantly, while no increased CD62p expression of platelets was observed after static incubation with PRP containing pCRP (60 μg/mL). Under flow conditions, perfusing immobilized ANCA-induced netting neutrophils with pCRP-containing PRP caused platelets activation and mCRP deposition. The newly generated mCRP induced platelets activation on ANCA-induced netting neutrophils, enhanced D-dimer formation, and enhanced high mobility group box 1 secretion by platelets.ConclusionsUnder flow conditions, ANCA-induced netting neutrophils can activate platelets and then prompt the formation of mCRP on activated platelets. Then the newly generated mCRP can further enhance the activation of platelets, the process of thrombogenesis, and the inflammatory response. So the high level of circulating pCRP is not only a sensitive marker for judging the disease activity, but also a participant in the pathophysiology of AAV.
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影响因子：
4.8
作者：
Ji, Shang-Rong;Wu, Yi;Zhao, Jing
通讯作者：
Zhao, Jing
影响因子：
7.3
作者：
Nakazawa D;Tomaru U;Yamamoto C;Jodo S;Ishizu A
通讯作者：
Ishizu A
DOI：
10.1161/atvbaha.108.174359
发表时间：
2008-12-01
影响因子：
8.7
作者：
Molins, Blanca;Pena, Esther;Badimon, Lina
通讯作者：
Badimon, Lina
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3.5
作者：
Maugeri, Norma;Franchini, Stefano;Manfredi, Angelo A.
通讯作者：
Manfredi, Angelo A.